Ubiquitination has been shown to be a critical step in various cellular processes, including cell division, signal transduction, neurotransmission, and development (Bonifacino and Weissman 1998; Kirkpatrick, Denison et al. 2005), yet elucidation of the proteins targeted by ubiquitination has been difficult because of the technical challenge in recovering modified proteins. The alteration of ubiquitination pathways and patterns of ubiquitination induces many neurodegenerative diseases, such as Alzheimer's disease, Parkinson disease, Huntington disease, and cancers, such as breast cancer, ovarian cancer, as well as numerous other conditions (Jiang and Beaudet 2004). Similarly patterns of ubiquitination can serve as a marker for these diseases or provide insight into the mechanism of diseases or the effects of experimental treatments on cells. Although the mechanisms of these diseases are not the same, all of them significantly alter ubiquitination pathways in one way or another, for example, by mutation, overexpression, or impairment in the function of proteins that directly or indirectly regulate ubiquitination. Ubiquitination can have significant effects on cellular function by affecting protein localization, protein-protein interactions, and protein turnover.
Unfortunately, not many ubiquitination sites have currently been identified in mammalian cells. Therefore, information on how to manipulate ubiquitination and modulate some of the processes involving ubiquitination is lacking. Furthermore, methods to profile ubiquitination in cells and tissues are lacking, and would require tools that allow for the simple, sensitive, specific, and rapid detection of ubiquitination sites in biological samples.